daa in the risk of recurrence after curative treatment of hcc

Conditions: Hepatocellular Carcinoma

Summary: for early stage of hcc, surgical resection or radiofrequency ablation (rfa) is the mainstay curative treatments. however, recurrence is still a major issue after the surgery or rfa. only selected patients are eligible and tolerable to ifn-based treatment after surgical resection and the sustained virological response varied. harvoni for genotype 1 hcv and sovaldi plus ribavirin for genotype 2 hcv can achieve high svr and being recommended by aasld and easl. mixed hcv genotype infection accounts for 10% of chc patients in taiwan. sovaldi-based treatment plus ribavirin should be as effective as sovaldi plus rivavirin in the treatment of genotype 2 hcv, as well as mixed genotype 1 and 2 hcv infection. as genotype 1 and 2 are the leading hcv genotypes in taiwan, it can simplify the regimen of anti-hcv treatment in taiwan by using harvoni plus ribavirin, not only for genotype 1 and 2 hcv but also for mixed genotype 1 and 2 hcv infection. although an unexpected high recurrence rate in hcc patients under daa treatment was reported once. however, one recent study showed a low risk of hcc recurrence after daa treatment. in this study, the investigators plan to enroll 130 hcv-hcc patients after confirming curative treatment for their hcc, either by surgery or rfa. for the cases fulfilling the inclusion/exclusion criteria, a 12 weeks harvoni plus ribavirin treatment will be provided for all cases (single armed design). the primary objective of the study is annual recurrence-free survival after curative resection of hcv-hcc for up to 5 years. a hospital-based cohorts of hcv-related hcc undergoing surgical resection or rfa from taipei veterans general hospital and investigated sites will be recruited as historical controls.

chronic hepatitis c virus (hcv) infection is a major etiology of hepatocellular carcinoma (hcc). for early stage of hcc, surgical resection or radiofrequency ablation (rfa) is the mainstay curative treatments. however, recurrence is still a major issue after the surgery or rfa. according to our previous report, the cumulated recurrence rate for small hcv-hcc was 72.4% at 5 year. peg-interferon plus rbv treatment is the standard of care for chronic hepatitis c (chc) in taiwan. nhird data showed that peg-ifn plus rbv treatment can reduce 12% of recurrence rate in 5 years (64% vs 52%) after curative resection of hcc. however, only selected patients are eligible and tolerable to ifn-based treatment after surgical resection and the sustained virological response varied. harvoni for genotype 1 hcv and sovaldi plus ribavirin for genotype 2 hcv can achieve high svr and being recommended by aasld and easl. all-oral regimen, being more tolerable and effective for hcc patients after curative treatment than ifn-based treatment. mixed hcv genotype infection accounts for 10% of chc patients in taiwan. sovaldi-based treatment plus ribavirin should be as effective as sovaldi plus rivavirin in the treatment of genotype 2 hcv, as well as mixed genotype 1 and 2 hcv infection. as genotype 1 and 2 are the leading hcv genotypes in taiwan, it can simplify the regimen of anti-hcv treatment in taiwan by using harvoni plus ribavirin, not only for genotype 1 and 2 hcv but also for mixed genotype 1 and 2 hcv infection. although an unexpected high recurrence rate in hcc patients under daa treatment was reported once. however, one recent study showed a low risk of hcc recurrence after daa treatment. harvoni is an all-oral regimen, being more tolerable and effective for hcc patients after surgery than ifn-based treatment. the all oral regimen would be beneficial in eradicating hcv viral load and subsequently reduce the risk of recurrence after curative resection of hcv-hcc. in this study, the investigators plan to enroll 130 hcv-hcc patients after confirming curative treatment for their hcc, either by surgery or rfa. for the cases fulfilling the inclusion/exclusion criteria, a 12 weeks harvoni plus ribavirin treatment will be provided for all cases (single armed design). the primary objective of the study is annual recurrence-free survival after curative resection of hcv-hcc for up to 5 years. the secondary objectives of the study are svr 4/12/24 by daa, regression of fibrosis, incidence of liver-related complications (ev bleeding, ascites) after daa treatment, and overall survival for 5 years. a hospital-based cohorts of hcv-related hcc undergoing surgical resection or rfa from taipei veterans general hospital and investigated sites will be recruited as historical controls. the historical controls include hcv-hcc undergoing curative treatment without peg-interferon plus ribavirin treatment (cohort 1) or with peg-interferon plus ribavirin treatment (cohort 2) after curative treatment (surgical resection or rfa) for hcc.

Eligibility criteria:
inclusion criteria: * anti-hcv positive and hbsag-negative * hcv genotype 1 or 2 infection, mixed infection gt 1 \& 2 is allowed * hcv rna ≥ 10,000 iu/ml at the time of screening * age \> 20 y/o * bclc stage 0 or a hcc confirmed by pathology and receiving the first time of curative treatment * no recurrence of hcc confirmed by contrast-enhanced image studies (ct or mri) within 3 months post the curative treatment. * performance status eastern cooperative oncology group (ecog) 0-1 * child-pugh score ≤7 exclusion criteria: * hbv, or hiv coinfection * co-existing other malignancy * intolerance to ribavirin * marked decompensated liver cirrhosis (ctp score\>7) * uremia or renal impaired patients (egfr\<30)

Keywords: chronic hepatitis c hepatocellular carcinoma direct-acting antiviral (daa) recurrence